ArticleThe Journal of biological chemistry2014
Down-modulation of SEL1L, an unfolded protein response and endoplasmic reticulum-associated degradation protein, sensitizes glioma stem cells to the cytotoxic effect of valproic acid.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Beyond Epilepsy Control: Repurposing Antiepileptic Drugs in Central Nervous System Tumor Therapy.Cells · 2026Review
- Downregulated TRAF3IP2-AS1 promotes hepatocellular carcinoma progression through the miR-374a-5p/SEL1L1/RPL6 axis to enhance DNA damage repair.American journal of translational research · 2025Article
- The unfolded protein response machinery in glioblastoma genesis, chemoresistance and as a druggable target.CNS neuroscience & therapeutics · 2024Review
- A Composite Bioinformatic Analysis to Explore Endoplasmic Reticulum Stress-Related Prognostic Marker and Potential Pathogenic Mechanisms in Glioma by Integrating Multiomics Data.Journal of oncology · 2022Article
- The Yin-Yang Dynamics in Cancer Pharmacogenomics and Personalized Medicine.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Human TERT promoter mutations as a prognostic biomarker in glioma.Journal of cancer research and clinical oncology · 2021Review
- Valproic Acid: A Promising Therapeutic Agent in Glioma Treatment.Frontiers in oncology · 2021Review
- Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment.Frontiers in oncology · 2020Review
- SEL1L plays a major role in human malignant gliomas.The journal of pathology. Clinical research · 2020Article
- The Epigenetics of Glioma Stem Cells: A Brief Overview.Frontiers in oncology · 2020Review
- Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors.Molecules (Basel, Switzerland) · 2018Review
- Implication of Endoplasmic Reticulum Stress in Autism Spectrum Disorder.Neurochemical research · 2018Review
- Translational gap in ongoing clinical trials for glioma.Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2018Review
- The construction of the multifunctional targeting ursolic acids liposomes and its apoptosis effects to C6 glioma stem cells.Oncotarget · 2017Article
- New insights into the unfolded protein response in stem cells.Oncotarget · 2016Review
- Endoplasmic reticulum quality control in cancer: Friend or foe.Seminars in cancer biology · 2015Review
- SEL1L SNP rs12435998, a predictor of glioblastoma survival and response to radio-chemotherapy.Oncotarget · 2015Article
- The Synergistic Effect of Combination Progesterone and Temozolomide on Human Glioblastoma Cells.PloS one · 2015Article
- Unfolded Protein Response and Cancer.Discoveries (Craiova, Romania) · 2014Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Valproic acid (VPA), an histone deacetylase inhibitor, is emerging as a promising therapeutic agent for the treatments of gliomas by virtue of its ability to reactivate the expression of epigenetically silenced genes. VPA induces the unfolded protein response (UPR), an adaptive pathway displaying a dichotomic yin yang characteristic; it initially contributes in safeguarding the malignant cell survival, whereas long-lasting activation favors a proapoptotic response. By triggering UPR, VPA might tip the balance between cellular adaptation and programmed cell death via the deregulation of protein homeostasis and induction of proteotoxicity. Here we aimed to investigate the impact of proteostasis on glioma stem cells (GSC) using VPA treatment combined with subversion of SEL1L, a crucial protein involved in homeostatic pathways, cancer aggressiveness, and stem cell state maintenance. We investigated the global expression of GSC lines untreated and treated with VPA, SEL1L interference, and GSC line response to VPA treatment by analyzing cell viability via MTT assay, neurosphere formation, and endoplasmic reticulum stress/UPR-responsive proteins. Moreover, SEL1L immunohistochemistry was performed on primary glial tumors. The results show that (i) VPA affects GSC lines viability and anchorage-dependent growth by inducing differentiative programs and cell cycle progression, (ii) SEL1L down-modulation synergy enhances VPA cytotoxic effects by influencing GSCs proliferation and self-renewal properties, and (iii) SEL1L expression is indicative of glioma proliferation rate, malignancy, and endoplasmic reticulum stress statuses. Targeting the proteostasis network in association to VPA treatment may provide an alternative approach to deplete GSC and improve glioma treatments.
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